Matthew K. Siggins
A5029119657- SARS-CoV-2 and COVID-19 Research
- Antimicrobial Resistance in Staphylococcus
- Streptococcal Infections and Treatments
- Viral gastroenteritis research and epidemiology
- COVID-19 Clinical Research Studies
- Salmonella and Campylobacter epidemiology
- Long-Term Effects of COVID-19
- Bacterial Infections and Vaccines
- Biochemical and Structural Characterization
- Bacterial Identification and Susceptibility Testing
- Vibrio bacteria research studies
- Microbial Metabolism and Applications
- Neonatal and Maternal Infections
- Sepsis Diagnosis and Treatment
- Genital Health and Disease
- Vaccine Coverage and Hesitancy
- Immune responses and vaccinations
- Influenza Virus Research Studies
- Dermatological and COVID-19 studies
- Infections and bacterial resistance
- SARS-CoV-2 detection and testing
- Antibiotic Use and Resistance
- COVID-19 Impact on Reproduction
- Bacterial biofilms and quorum sensing
- Nosocomial Infections in ICU
Imperial College London
2015-2024
University of Birmingham
2011-2021
St Mary's Hospital
2021
Hammersmith Hospital
2016
Immune Regulation (United Kingdom)
2011-2013
Medical Research Council
2011-2013
Novartis (Italy)
2013
While it is now widely accepted that host inflammatory responses contribute to lung injury, the pathways drive severity and distinguish coronavirus disease 2019 (COVID-19) from other viral diseases remain poorly characterized. We analyzed plasma samples 471 hospitalized patients recruited through prospective multicenter ISARIC4C study 39 outpatients with mild disease, enabling extensive characterization of across a full spectrum COVID-19 severity. Progressive elevation levels numerous...
Human infection challenge permits in-depth, early, and pre-symptomatic characterization of the immune response, enabling identification factors that are important for viral clearance. Here, we performed intranasal inoculation 34 young adult, seronegative volunteers with a pre-Alpha severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain. Of these participants, 18 (53%) became infected showed an interferon-dominated mediator response divergent kinetics between nasal systemic...
Patients with acute liver failure (ALF) have systemic innate immune suppression and increased susceptibility to infections. Programmed cell death 1 (PD-1) expression by macrophages has been associated during sepsis cancer. We therefore examined the role of programmed 1/programmed ligand (PD-1/PD-L1) pathway in regulating Kupffer (KC) inflammatory antimicrobial responses acetaminophen-induced (APAP-induced) injury. Using intravital imaging flow cytometry, we found impaired KC bacterial...
The complement cascade is crucial for clearance and control of invading pathogens, as such a key target pathogen mediated host modulation. C3 the central molecule cascade, plays vital role in opsonization bacteria recruitment neutrophils to site infection. Streptococcal species have evolved multiple mechanisms disrupt complement-mediated innate immunity, among which ScpA (C5a peptidase), C5a inactivating enzyme, widely conserved. Here we demonstrate first time that pyogenic streptococcal are...
Salmonella enterica serovar Typhi expresses a capsule of Vi polysaccharide, while most serovars, including S. Enteritidis and Typhimurium, do not. Both express the lipopolysaccharide O:9 antigen, yet there is little evidence cross-protection from anti-O:9 antibodies. Vaccines based on polysaccharide have efficacy against typhoid fever, indicating that antibodies confer protection. Here we investigate role in antibody-dependent complement- phagocyte-mediated killing Salmonella. Using isogenic...
Complement, a critical defence against pathogens, has been implicated as driver of pathology in COVID-19. Complement activation products are detected plasma and tissues complement blockade is considered for therapy. To delineate roles immunopathogenesis, we undertook the largest comprehensive study COVID-19 to date, profiling 16 biomarkers, including key components, regulators products, 966 samples from 682 hospitalized patients collected across hospitalization period part UK ISARIC4C...
Abstract Nontyphoidal strains of Salmonella are a major cause fatal bacteremia in Africa. Developing vaccine requires an improved understanding the relevant mechanisms protective immunity, and mouse model infection is useful for studying immunity to vivo. It important appreciate similarities differences between mice men. Ab protection against nontyphoidal both species, we have previously found role cell-free complement-mediated bactericidal activity Africans. unclear whether this modality...
Unassisted metastasis through the lymphatic system is a mechanism of dissemination thus far ascribed only to cancer cells. Here, we report that Streptococcus pyogenes also hijack vessels escape local infection site, transiting sequential lymph nodes and efferent enter bloodstream. Contrasting with previously reported mechanisms intracellular pathogen carriage by phagocytes, show S. remain extracellular during transit, first in afferent then lymphatics carry bacteria successive draining...
Systemic bacterial infection is typically attributed to direct blood vessel invasion or intracellular transit, while the role of lymphatic system remains largely unexplored. We previously showed that Streptococcus pyogenes disseminates extracellularly via lymphatics. Here, we extend this observation a diverse group important extracellular pathogens, including Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, and agalactiae. In murine soft tissue model,...
Abstract Admission procalcitonin measurements and microbiology results were available for 1040 hospitalized adults with coronavirus disease 2019 (from 48 902 included in the International Severe Acute Respiratory Emerging Infections Consortium World Health Organization Clinical Characterisation Protocol UK study). Although was higher bacterial coinfection, this neither clinically significant (median [IQR], 0.33 [0.11–1.70] ng/mL vs 0.24 [0.10–0.90] ng/mL) nor diagnostically useful (area...
Summary Background Most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal plasma antibody responses one year after hospitalisation for COVID-19, including a period when vaccination was introduced. Methods Plasma nasosorption samples were prospectively collected from 446 adults hospitalised COVID-19 between February 2020 March 2021 via the ISARIC4C PHOSP-COVID...
Nontyphoidal Salmonellae commonly cause fatal bacteraemia in African children lacking anti-Salmonella antibodies. These are facultative intracellular bacteria capable of cell-free and survival within macrophages. To better understand the relationship between extracellular infection blood general mechanisms Ab-related protection against Salmonella, we used human sera to measure kinetics Ab complement deposition, serum-mediated bactericidal killing phagocytosis invasive Salmonella enterica...
Staphylococcus aureus is a human commensal organism and opportunist pathogen, causing potentially fatal disease. The presence of non-pathogenic microflora or their components, at the point infection, dramatically increases S . pathogenicity, process termed augmentation. Augmentation associated with macrophage interaction but by hitherto unknown mechanism. Here, we demonstrate breadth cross-kingdom microorganisms can augment disease that pathogenesis Enterococcus faecalis also be augmented....
Abstract Background While inflammatory and immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in peripheral blood are extensively described, at the upper mucosal site of initial relatively poorly defined. We sought identify cytokine/chemokine signatures that distinguished disease 2019 (COVID-19) severity categories, relate these progression inflammation. Methods measured 35 cytokines chemokines nasal samples from 274 patients hospitalized with...
Staphylococcal toxic shock syndrome (TSS) is a life-threatening illness causing fever, rash, and shock, attributed to toxins produced by the bacterium Staphylococcus aureus , mainly toxin 1 (TSST-1). TSS was in past commonly linked with menstruation high-absorbency tampons; now, more frequently triggered other staphylococcal infections, particularly of skin soft tissue. Investigating progress treatment patients challenging, as rare; animal models do not mimic adequately, interact best human...
The range of exoproteins and core exoproteome 14 Staphylococcus aureus isolates representing major lineages associated with asymptomatic carriage clinical disease in the UK was identified by MS proteomics using a combined database incorporating sequences derived from 39 S. genomes. In all, 632 different proteins were and, these, only 52 (8 %) found all whereas 144 (23 just single isolate. Comparison observed mass each protein (based on migration SDS-PAGE) its predicted amino acid sequence)...
Introductory paragraph The mechanisms that underpin COVID-19 disease severity, and determine the outcome of infection, are only beginning to be unraveled. host inflammatory response contributes lung injury, but circulating mediators levels fall below those in classical ‘cytokine storms’. We analyzed serial plasma samples from 619 patients hospitalized with recruited through prospective multicenter ISARIC clinical characterization protocol U.K. study 39 milder community cases not requiring...
Invasive group A Streptococcus (iGAS) is frequently associated with emm1 isolates, an attendant mortality of around 20%. Cases occasionally arise in previously healthy individuals a history upper respiratory tract infection, soft tissue contusion, and no obvious portal entry. Using new murine model we determined the impact contusion on iGAS bacterial burden phenotype.Calibrated mild blunt did not provide focus for initiation or seeding GAS that was detectable following systemic bacteremia,...
Abstract Human infection challenge permits characterisation of the associated immune response in unparalleled depth, enabling evaluation early pre-symptomatic changes and dynamic factors important for viral clearance. Here, 34 healthy young adult volunteers, seronegative to SARS-CoV-2, were inoculated with a D614G-containing pre-Alpha SARS-CoV-2 strain. Nasal systemic soluble mediator antibody responses, peripheral blood T cell B responses measured by MesoScale Discovery flow cytometry just...